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Survival analysis of all 13 patients was carried out with a Kaplan–Meier survival estimate.
This journal is a member of and subscribes to the principles of the Committee on Publication Ethics. In summary, the cumulative radiation doses were 68–78 Gy to the primary tumour, 60–74 Gy to involved areas of the neck, and 50 Gy to low-risk local areas. 2 (clinical target volumes 1 and 2)—were contoured on magnetic resonance images (Figure 1). 1 with 5- to 10-mm margins (forward, both sides, up and down) and a 3- to 5-mm margin (back). After completion of treatment, patients were assessed every 3 months during the first 2 years, every 6 months for the 3 subsequent years, and annually thereafter in clinic visits, telephone interviews, or written correspondence. Kaplan–Meier curves for (A) overall survival, (B) locoregional failure-free survival, (C) distant failure-free survival, and (D) failure-free survival for the study groups.
Multivariate analysis with the Cox proportional hazards model was used to evaluate the prognostic values of age, sex, World Health Organization histology, disease stage, T stage, N stage, chemotherapy regimen, and radiotherapy technology. 26–28, effective treatment of distant metastases remains an important problem to be solved. Targeted therapy has become a popular method of tumour treatment, and its addition to standard chemotherapy might reduce treatment failures from distant metastases.
We thank Ying Chen from the Department of Administration, Office of Disease Process, for help with follow-up.
The authors declare no financial conflicts of interest regarding the design or results of this study. Correspondence to: Xiaodong Zhu, Department of Radiation Oncology, The Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, 71 He Di Road, Nanning 530021 PR China. The endpoints included overall survival, locoregional failure-free survival, distant metastasis failure-free survival, and failure-free survival.
Multivariate analyses indicated that only tumour stage was a prognostic factor for overall survival.
There were no significant differences between the groups in age, sex, Karnofsky score, histologic type, T stage, N stage, overall stage, or chemotherapy administered (Table i). All patients were immobilized in the supine position with a thermo-plastic head–neck–shoulder mold and a head-and-neck immobilization board.
The information obtained was used to assess patient survival, patterns of relapse, incidence of distant metastasis, and other clinical symptoms. The chi-square test was used for comparisons of categorical data such as sex, Karnofsky score, histologic type, T stage, N stage, overall stage, and chemotherapy regimen. In the present study, 17 patients experienced a locoregional or neck relapse, and 32 patients developed distant metastasis.
First, being a nonrandomized controlled study, it included patients only if they met specific selection criteria. Patient profile and survival in 270 computer tomography–staged patients with nasopharyngeal cancer treated at the Singapore General Hospital.
Prognostic factors in 677 patients in Singapore with nondisseminated nasopharyngeal carcinoma. Significant prognosticators after primary radiotherapy in 903 nondisseminated nasopharyngeal carcinoma evaluated by computer tomography.
Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase iii randomized Intergroup study 0099. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma [Chinese].
Comparison of concurrent chemoradiotherapy followed by adjuvant chemotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a meta-analysis of 793 patients from 5 randomized controlled trials. Factors contributing to the efficacy of concurrent–adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma: combined analyses of npc-9901 and npc-9902 trials. Comparison of clinical outcomes between concurrent chemoradiotherapy followed by adjuvant chemotherapy and concurrent chemoradiotherapy alone for patients associated with locally advanced nasopharyngeal carcinoma: a retrospective analysis of single center experience [abstract e16003].
Phase iii study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival. The role of concurrent chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma among endemic population: a meta-analysis of the phase iii randomized trials. Phase iii study comparing standard radiotherapy with or without weekly oxaliplatin in treatment of locoregionally advanced nasopharyngeal carcinoma: preliminary results.
Concurrent chemoradiotherapy versus radiotherapy alone for locoregionally advanced nasopharyngeal carcinoma. The role of concurrent chemoradiation to radiotherapy alone in the treatment of locally advanced nasopharyngeal carcinoma: a meta-analysis of the phase iii randomized trials. A phase iii randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. Carboplatin plus Taxol is an effective third-line regimen in recurrent undifferentiated nasopharyngeal carcinoma.
Experience with combination of cisplatin plus gemcitabine chemotherapy and intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma.


Comparing treatment outcomes of different chemotherapy sequences during radio-chemotherapy for stage N3 nasopharyngeal carcinoma. A multicenter randomized controlled trial (rct) of adjuvant chemotherapy (ct) in nasopharyngeal carcinoma (npc) with residual plasma ebvdna (ebvdna) following primary radiotherapy (rt) or chemoradiotherapy (crt) [abstract 5511].
A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. Intensity modulated conformal radiation therapy and clinical efficacy of conventional radiotherapy combined with chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma [Chinese].
A randomized trial of induction chemotherapy plus concurrent chemoradiotherapy versus induction chemotherapy plus radiotherapy for locoregionally advanced nasopharyngeal carcinoma. Long-term survival of nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy. Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer: Results of a 4-year multicenter randomized study.
Study of tpf neoadjuvant chemotherapy followed by concurrent intensity modulated radiochemotherapy in the treatment for 30 cases with locally advanced nasopharyngeal carcinoma. Efficacy of induction chemotherapy combined with concurrent chemoradiotherapy for advanced nasopharyngeal carcinoma. Multicenter safety study on cetuximab combined with intensity modulated radiotherapy and concurrent chemotherapy of cisplatin in locoregionally advanced nasopharyngeal carcinoma.
The protocol for this retrospective study was approved by the Ethics Committee of the Cancer Hospital of Guangxi Medical University. Follow-up computed tomography imaging (2.5-mm slice thickness) of the head and neck, extending from the calvarium to the supraclavicular region, was conducted by a radiologic technician.
Follow-up examinations included chest radiography or computed tomography, ultrasonography of liver and abdomen, whole-body bone scan, computed tomography or magnetic resonance imaging of the head and neck, and fibrotic endoscopy with or without biopsy. Development of distant metastases was the primary reason for treatment failure, and similar results have been found in other trials29,30. The addition of antiangiogenic agents to a primary treatment has also been speculated to possibly result in sterilization of distant micrometastases. Second, the relatively short follow-up period might limit proper prediction of long-term results. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC) treatment.
Patients were first treated with two lateral opposing facial–cervical fields, with the lower cervical supraclavicular anterior tangential fields set to deliver 36 Gy. Finally, the small sample size might have resulted in an inadequate number of events for a proper analysis of results.
We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC.MethodsBetween 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Patients were then treated with two shrinking lateral opposing facial–cervical fields, with the lower cervical supraclavicular anterior tangential and posterior cervical fields administering beta irradiation. Zhongguo Liang and Xiaodong Zhu contributed equally to this study and should be considered co– first authors of this report. In the third phase, preauricular portal and posterior cervical beta irradiation fields were used to avoid further irradiation of the spinal cord. Using a Cox proportional hazard model, patients with NPC treated by high-volume physicians (caseload a‰? 35) had better survival rates (p = 0.001) after adjusting for comorbidities, hospital, and treatment modality. A booster dose of irradiation (6–10 Gy in 3–5 fractions) was delivered to the base of the skull if the skull base and intracranial extension showed tumour involvement. In cases in which the patient showed nasal and ethmoidal involvement, an anterior facial electron field was added. The "practice makes perfect" hypothesis may be valid for certain procedures such as open-heart and vascular surgery and "selective referral" may in part account for this phenomenon [3, 4].
However, such a positive volume-outcome relationship is not well validated for other procedures. Radiotherapy or concurrent chemoradiotherapy (CCRT) is the principal treatment because NPC is anatomically inaccessible and highly sensitive to radiotherapy and chemotherapy [8].Previous volume-outcome studies have shown improved treatment outcome in breast cancer, oral cancer, esophageal cancer, radical prostatectomy, and nephrectomy [5, 9a€“11].
The purpose of this study was to examine the relationship between physician caseload and survival rate in NPC using population-based data.In most previous studies on the association between caseload and outcome, a Cox proportional hazards model or logistic regression was routinely used, raising the possibility that selection bias might still exist. Therefore, we evaluated the association between physician caseload and survival rate using population-based data, Cox regression analysis, and propensity score to minimize the effect of selection bias.Patients and methodsThe database contained a registry of contracted medical facilities, a registry of board-certified physicians, and monthly claims summary for all inpatient claims. Patients with unclear treatment modality and incomplete physician data or treated by physicians with a very small caseload (less than 4 cases within 3 years) were excluded. Finally, 1225 patients treated by 98 radiation oncologist during this period were included.Physicians were further sorted by their total patient volume using the unique physician identifiers in this database and by their caseload of NPC patients. Patient characteristics included age, gender, geographic location, treatment modality, severity of disease, and enrollee category (EC). The disease severity in each patient was assessed using the modified Charlson Comorbidity Index score, which has been widely used in recent years for risk adjustment in administrative claims data sets [14].This study used EC as a proxy measure of socioeconomic status, which is an important prognostic factor for cancer patients [15, 16].
Propensity score stratification replaces the many confounding factors that may be present in an observational study with a variable of these factors. To calculate the propensity score, patient characteristics in this study were entered into a logistic regression model predicting selection for high-volume surgeons. These characteristics included year in which the patient was diagnosed, age, gender, Charlson Comorbidity Index score, geographic area of residence, enrollee category, and treatment modality.


The study population was then divided into five discrete strata on the basis of propensity score.
The effect of caseload assignment on 10-year survival rate was analyzed within each quintile. The Mantel-Haenszel odds ratio was calculated in addition to the Cochran-Mantel-Haenszel I‡2 statistic.ResultsA total of 423 patients (35%) died out of 1225 patients who underwent curative treatment between 1998 and 2000. Patients in the high-volume physician group were more likely to undergo radiotherapy, reside in Northern Taiwan, have lower comorbidity score, and better enrollee category than their counterparts in other groups. There were 74 radiation oncologists (76%) in the low-volume group, 17 physicians (17%) in the medium-volume group, and 7 (7%) physicians in the high-volume group.
Table 3 shows the adjusted hazard ratios calculated using the Cox proportional hazards regression model after adjusting for patient comorbidities, hospital type, and treatment modality. The positive association between survival and physician caseload remained statistically significant in multivariate analysis. In each of the five strata, patients treated by high-volume physicians had a higher 10-year survival rate. After controlling for patient characteristics and other variables in the Cox proportional regression model, the adjusted hazard ratio was 0.6 for high-volume physicians, indicating that patients with NPC treated by high-volume physicians had a lower risk of death and were more likely to live longer. The results of both forms of analyses led to the conclusion that the 10-year survival rates for patients with NPC treated by high-volume physicians were significantly better.Previous studies have evaluated the benefits of high hospital and physician volume on the outcomes of cancer treatment. In our series, we also found a better 10-year survival rate associated with treatment by high-volume physicians.The quality of the risk-adjustment technique in analyzing administrative information is an important issue. We found treatment by high-volume physicians was significantly associated with lower adjusted hazard ratio for death.
Patients treated by high-volume physicians were found to have a 40% lower risk of death after adjusting for comorbidities and other confounding factors. In the second part of our series, propensity score was used to stratify patients into five strata with similar propensity score in order to reduce the effect of selection bias on caseload groups [19a€“21]. In order to explore the caseload effect of radiotherapy on NPC survival, we calculated the caseload volume of radiation oncologists. In agreement with previous volume-outcome studies, our results indicated that increased caseload of radiation oncologists is associated with improved outcomes after other factors.Several hypotheses relating to the volume-outcome relationship have been proposed.
The "practice makes perfect" concept suggests that increased caseload may help physicians or hospital staff improve the execution of treatment procedures, such as planning the radiation field and manipulation of the radioactive source of teletherapy units.
The role of surgery in the treatment of NPC is limited, and carefully defining the planning target volume with the aid of CT or MRI images is important for radiotherapy or concurrent chemoradiotherapy in NPC.
A high-volume team may be more adept at administering a radiation dose, with or without a booster dose, that balances the benefit of successful loco-regional control against the risk of radiation toxicity.Previous study reported that high-volume physicians use effective treatment and strategies more often than do low-volume physicians [22]. In breast cancer series, high-volume surgeons adopted a multi-disciplinary approach whereas low-volume surgeons were less likely to interact with oncologists or attend multi-disciplinary meetings [23]. Use of multidisciplinary approaches may account for the better outcomes achieved by high-volume physicians. Possibly, low-volume physicians do not always follow the international guidelines for NPC treatment.The "selective referral hypothesis" postulates that healthier patients or patients with early-stage disease tend to be referred to high-volume physicians. The referral system in Taiwan is weakly enforced, and people are free to choose any physician. Because official performance information to help consumers select healthcare providers is not available, patients choose physicians with better reputations or more successful physicians after consulting with their relatives and friends [4].
Selective referral bias may also result from the referral of more curable patients to high-volume physicians. Patients not seeking curative treatment or for whom curative treatment is not possible may continue to receive their care from low-volume physicians.Our study revealed some issues that may be useful for policy makers. Research is needed to identify the differences in care and treatment strategy between low-, medium-, and high-volume physicians. The viewpoints of high-volume physicians may influence the development of effective protocols and practice guidelines for the majority of clinical situations.
The treatment strategies of high-volume physicians should be analyzed and adopted throughout the country to improve survival rates.Our study has several limitations. First, we could not assess the relationship of caseload to NPC stage because this information was not available from the database. However, Begg et al., using a SEER-Medicare linked database, reported that cancer stage and patient age were independent of caseload volume [24].
Instead of cancer-specific survival rates, overall survival rate was used, because it was not possible to determine cause-specific mortality based on the registry data.
Given the robustness of the evidence and statistical analysis in this study, these limitations are unlikely to compromise our results.In summary, our findings support the conclusion that provider volume affects survival outcome in NPC.
Analysis using a Cox proportional hazard model and propensity score found an association between high-volume physicians and improved 10-year survival rate in patients with NPC.



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